Normal metabolic and abnormal pathological roles of free radicals and reactive oxygen species serve as the focus of Dr. Kagan’s laboratory. Dr. Kagan is interested in both (i) the mechanisms involved in the enhance radical generation by physical and chemical factors (e.g. UV-irradition, transition and heavy metals, carcinogens, tumor necrosis factor, among others) and pathological conditions (e.g. ischemia/reoxigenation of the heart and brain), and (ii) the effects of these factors on endogenous antioxidants.

 

Specifically, three major research directions currently in Dr. Kagan’s laboratory are 1) Role of phenoxyl radicals in cytotoxicity of phenolic compounds. Strategies are being developed to enhance antitumor activity by modulating free radical metabolism of cytotoxic drugs (e.g. etoposide). 2) Role of antioxidant and prooxidant interactions of hemoglobin with nitric oxide during hemorrhage-induced oxidative injury. 3) Development of novel, sensitive and accurate methods for quantitation of oxidative stress.

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Important Publications

Basova LV, IV Kurnikov, L Wang, VB Ritov, NA Belikova, II Vlasova, AA Pacheco, DE Winnica, J Peterson, H Bayir, DH Waldeck and VE Kagan. Cardiolipin switch in mitochondria: Shutting off the reduction of Cytochrome c and turning on the peroxidase ectivity. Biochemistry 46(11):3423-3434, 2007.

Tyurina YY, LV Basova, NV Konduru, VA Tyurin, AI Potapovich, P Cai, H Bayir, D Stoyanovsky, BR Pitt, AA Shvedova, B Fadeel and VE Kagan. Nitrosative stress inhibits the aminophospholipid translocase resulting in phosphatidylserine externalization and macrophage engulfment: Implications for the resolution of inflammation. J Biol Chem 282(11):8498-8509, 2007.

Tyurina YY, V Kini, VA Tyurin, II Vlasova, J Jiang, AA Kapralov, NA Belikova, JC Yalowich, IV Kurnikov and VE Kagan. Mechanisms of cardiolipin oxidation by cytochrome c: Relevance to pro- and antiapoptotic functions of etoposide. Mol Pharmacol 70(2):706-717, 2006.

Vlasova II, VA Tyurin, AA Kapralov, IV Kurnikov, AN Osipov, MV Potapovich, DA Stoyanovsky and VE Kagan. Nitric oxide inhibits peroxidase activity of cytochrome c.cardiolipin complex and blocks cardiolipin oxidation. J Biol Chem 281(21):14554-14562, 2006.

Kagan VE, VA Tyurin, J Jiang, YY Tyurina, VB Ritov, AA Amoscato, AN Osipov, NA Belikova, AA Kapralov, V Kini, II Vlasova, Q Zhao, M Zou, P Di, DA Svistunenko, IV Kurnikov and GG Borisenko. Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol 1(4):223-232, 2005.